Radiation damage will be determined in biologically active molecules as models for the primary effects in vivo. The effects of the aqueous radicals will be studied by irradiating substrates in solution in the presence of specific radical scavengers so that the action of the reactive species H., .OH, e minus aq, HO2. and O minus 2 can be evaluated separately. Amino acids, in particular the sulfur-containing and aromatic residues, will be irradiated separately, as mixtures and when incorporated into peptides of increasing complexity. Peptides and proteins will be studied for the efficiency and specificity of action of the individual radicals for loss of biological activity, destruction of amino acids and changes in molecular configuration. Ribonuclease and ribonuclease S-peptide are currently under investigation. Chromatin, extracted from cultured mammalian cells, will be examined for radiation damage in the DNA and associated proteins. Changes in molecular configuration of DNA are being determined from the sedimentation behavior on alkaline sucrose gradients and hence an estimate of the number of single-strand breaks made. Irradiated chromatin will be examined for the formation of covalent linkages between DNA and protein. Proteins will be analyzed for changes in amino acid composition and polyacrylamide gel electrophoresis used to characterize the histones. In addition, a search will be made for chemical modification in the constituent nucleic acids.